Effects of vasoactive substances released from ischemic reperfused liver on the isolated rat heart.

Background: Cardiovascular dysfunction frequently occurs after major vascular surgery or liver transplantation.

Objective: To evaluate the effects on myocardial activity of vasoactive agents released from ischemic-reperfused liver.

Animals And Methods: Isolated rat livers were perfused with Krebs-Henseleit solution (KH), propranolol 10(-5) M, losartan 2x10(-5) M and indomethacin 10(-5) M, then made globally ischemic for 120 min (37 degrees C) and reperfused. Isolated hearts from other rats were stabilized with KH and reperfused for 15 min with the perfusate exiting the livers. Livers were disconnected, and the hearts continued to be recirculated with the accumulated liver and heart effluent for an additional 50 min. Enzyme leakage, different vasoactive substances, left ventricular developed pressure (LVP) and coronary flow were measured during the experimental protocol.

Results: Hepatic release of adrenaline, noradrenaline, angiotensin II, prostaglandin E(2) and thromboxane B(2) was significantly increased in the liver effluent following ischemia. When this effluent was directed to the heart, LVP was significantly raised in the first 10 min of reperfusion (137+/-5%) followed by marked decreased (46+/-6%) during the following 65 min of myocardial reperfusion. In the ischemic-reperfused drug-treated groups, the initial positive effect on LVP was milder than in controls (propranolol 112+/-12%, losartan 111+/-11%, indomethacin 113+/-9%) and the final LVP was lower (propranolol 29+/-6%, losartan 27+/-7% [P<0.05 versus ischemic control], indomethacin 46 +/-12%).

Conclusion: During the initial phase of reperfusion, vasoactive substances released in the hepatic effluent potentiated LVP of the hearts exposed to this effluent. When the three inhibitory drugs were added to KH, this initial augmentation was not sustained. Propranolol and losartan, but not indomethacin, further depressed LVP. Vasoactive substances released from ischemic reperfused livers directly influenced heart function.